The objectives of this proposal are to evaluate the need for creatine and phosphocreatine in skeletal muscle by determining the consequences of specifically depleting muscle of these compounds and to answer the question: Do abnormalities of creatine metabolism cause disease of muscle? Depletion will be accomplished by feeding Beta-guanidinobutyric acid, an inhibitor of creatine transport into muscle which does not serve as a substrate for creatine kinase, or by feeding Beta-guanidinopropionic acid, an inhibitor of creatine transport which is phosphorylated by creatine kinase to yield a poor artificial phosphagen to replace phosphocreatine in muscle. The ability of muscle to withstand his depletion will be evaluated in long term studies and in studies of the responses of the superimposed stresses of thyrotoxicosis, vitamin E deficiency, and hereditary muscular dystrophy. The function and metabolism of depleted muscle will be studied using intact muscles at rest, during contraction, and during recovery from contraction. Particular attention will be paid to the putative role of phosphocreatine in the control of glycolysis.